tbuckley/cabot-search huggingface dataset:
AB0704 EVALUATION OF THE OF THE 2022 ACR/EULAR CLASSIFICATION CRITERIA FOR GCA IN A GERMAN PATIENT COHORT
Authors: R. Bergner, P. Schulz, J. Friedrich
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> In 2022, the ACR and the EULAR proposed new classification criteria for Giant Cell Arteritis (GCA). While the previous classification criteria from 1990 were based on clinical and histological findings only, the new classification criteria also consider several types of imaging. <h3>Objectives</h3> To assess and compare the sensitivity and specificity of the ACR 1990 (1990CC) and the ACR/EULAR-2022 classification criteria (2022CC) for GCA. <h3>Methods</h3> In a retrospective analysis, we classified 210 patients (33 % males, median age 68 years) with suspected GCA according to the 1990CC and 2022CC. All patients attended the Klinikum Ludwigshafen between 2018 and 2022 and were examined with either ultrasound, MRI, or PET-CT. The results were compared with the final clinical diagnosis made by the attending physician. <h3>Results</h3> Of 210 patients under consideration, 94 had GCA. Of these 94 patients, 54 met the 1990CC, while 90 met the 2022CC (Table 1). Of the 116 non-GCA patients, 110 did not meet the 1990CC and 112 did not meet the 2022CC, amounting to a sensitivity and specificity of 0.57 and 0.96 for the 1990CC versus 0.96 and 0.97 for the 2022CC, respectively (Table 1). Overall, the correct classification proportion was 0.78 for the 1990CC and 0.96 for the 2022CC (Table 1). It was noticeable that 21 GCA patients had no cranial symptoms like temporal headache, jaw claudication, or striking temporal arteries. 18 of these patients were correctly classified by the 2022CC, but all of them were misclassified by the 1990CC. Moreover, 81 of 94 patients showed a typical ultrasound halo in at least one vessel section, which increased the sensitivity of the 2022CC. <h3>Conclusion</h3> Our results demonstrate that the inclusion of imaging methods increase the sensitivity of the 2022CC compared with the 1990CC, while the specificity of &gt; 0.95 remains similar. The 1990CC were primarily developed for the classification of giant cell temporal arteritis, causing a frequent misclassification of patients with isolated extracranial large vessel vasculitis. Moreover, the 1990CC classified GCA patients without cranial symptoms only accurately in case of a positive temporal biopsy. <h3>References</h3> Hunder GG, Bloch DA, Michel BA. et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990;33:1122–1128. Ponte C, Grayson PC, Robson JC, et al. 2022 American College of Rheumatology/EULAR classification criteria for giant cell arteritis. Ann Rheum Dis. 2022;81(12):1647-1653 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Raoul Bergner Speakers bureau: Abbvie, Bristol Myers Squibb, Chugai, Glaxo Smith Kline, Galapagos, MSD, Novartis, Consultant of: Galapagos, Vifor, Patricia Schulz: None declared, Julian Friedrich: None declared.
POS1141 SUBTHERAPEUTIC HYDROXYCHLOROQUINE CONCENTRATION IS ASSOCIATED WITH INCREASED DISEASE ACTIVITY AND GREATER ORGAN DAMAGE DURING 5-YEAR FOLLOW-UP IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: S. S. Lee, J. H. Kang, S. E. Choi, D. J. Park
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background:</h3> <h3>Objectives</h3> Hydroxychloroquine (HCQ) is a cornerstone drug in patients with systemic lupus erythematosus (SLE), as it decreases the risk of flares and comorbidities and improves survival. This study investigated the effects of the serum HCQ concentration on clinical manifestations, disease activity, and organ damage in a longitudinal cohort of SLE patients. <h3>Methods</h3> The 338 SLE patients from the Korean Lupus Network registry were assessed with respect to their demographic data, clinical and laboratory findings, PGA score, and adjusted mean SLEDAI-2000 (AMS) and SLICC damage index scores annually for 5 consecutive years. Patients were divided into two groups according to their serum HCQ concentration at baseline: patients with a subtherapeutic level (&lt; 500 ng/mL) and those with a therapeutic level (try were assessed with respect to their demographion the clinical outcomes was evaluated in a longitudinal analysis using a generalized estimating equation (GEE) and a logistic regression analysis. <h3>Results</h3> Of the 338 patients, 287 (84.9%) were in the subtherapeutic group at baseline. This group had a higher incidence of newly developed lupus nephritis (P = 0.036) and had been prescribed higher mean and cumulative doses of prednisolone (P = 0.003 and P = 0.013) than the therapeutic group. In multivariable analyses based on GEE, an association of the subtherapeutic group with both a higher PGA score (β coefficient = 0.328, 95% confidence interval [CI]: 0.215–0.441, P &lt; 0.001) and a higher SLICC damage index score (β coefficient = 0.366, 95% CI: 0.061–0.671, P = 0.019) was determined across all 5 years. In the multivariate logistic regression analysis, subtherapeutic HCQ was significantly associated with the AMS (odds ratio [OR] = 1.142, 95% CI 1.022–1.276, P = 0.019), mean PGA (OR = 3.697, 95% CI 1.767–7.735, P &lt; 0.001), and an annual increase in the SLICC damage index score (OR = 1.529, 95% CI 1.005–2.325, P = 0.047). <h3>Conclusion</h3> A subtherapeutic HCQ concentration may affect the development of new-onset LN, and had the significant association with higher disease activity and cumulative organ damage in these SLE patients over time. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0022 IL-23 POSITIVE NEUTROPHIL IS THE MAIN CELL SUBTYPE IDENTIFIED FROM SYNOVIAL FLUID OF PSORIATIC ARTHRITIS WITH THE POTENTIATION OF NEUTROPHIL EXTRACELLULAR TRAPS FORMATION
Authors: Y. P. Tsao, S. T. Chen
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Psoriatic arthritis (PsA) is a systemic autoimmune disease. Interleukin-23 (IL-23) and IL-17 are two main cytokines involving in the pathogenesis of psoriasis (PsO) and PsA. The origin and maintenance of IL-23 is the stakeholder of disease progression in PsA and should be carefully evaluated. <h3>Objectives</h3> To validate the role of neutrophils in maintaining the inflammation in PsA joint. <h3>Methods</h3> Synovial fluid from PsA was obtained from swelling knee joints, and the immune cells were classified by flowcytometry. The IL-23 positive cells were evaluated with marker of CD66b, CD14, and CD16. Neutrophils from healthy donor were collected and treated with interferon-α (IFN-α) and proteoglycan (PGN) for mimicking the neutrophils activation in PsO/PsA patients. Subsequent evaluation neutrophil extracellular traps (NETs) formation was conducted. <h3>Results</h3> 10 PsA joints fluid was collected. Among active and chronic PsA synovial fluid, neutrophil is the most abundant cell type identified among IL-23 positive cells (ranging from 65-90%). The t-SNE plot for mapping the repertoire of IL-23 containing cells confirmed the majority cell subtype with CD66b+ positive neutrophils. After stimulating neutrophils from healthy donor with IFN-α and PGN revealed increasing IL-23p19 expression after 16 hours stimulation. The NETs formation is profound and IL-23p19 containing NETs material could be identified. <h3>Conclusion</h3> IL-23 containing CD66b+ neutrophil is the main cell type in synovial fluid of PsA, which might be activated by inflammatory factors and release IL-23 with NETs material to promote type 17 T cell differentiation in joints. <h3>References</h3> [1]Schinocca C, Rizzo C, Fasano S, Grasso G, La Barbera L, Ciccia F, et al. Role of the IL-23/IL-17 pathway in rheumatic diseases: an overview. Frontiers in immunology. 2021;12:637829. [2]Suzuki E, Mellins ED, Gershwin ME, Nestle FO, Adamopoulos IE. The IL-23/IL-17 axis in psoriatic arthritis. Autoimmun Rev. 2014;13:496-502. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0539 ANIFROLUMAB FOR REFRACTORY SKIN DISEASE IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): A SINGLE CENTER CASE SERIES
Authors: S. Flouda, E. Sampatakaki, G. S. Moysidou, M. Kosmetatou, K. Kouna, D. Katsifis Nezis, A. Filippopoulou, K. Zoupidou, P. Katsimpri, D. Boumpas, A. Fanouriakis
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Anifrolumab (ANI) a human monoclonal antibody to type I interferon receptor subunit 1 has been recently approved for the treatment of SLE. In SLE, the skin is not only a target but also a key- driver of the autoimmune response via the production of type I IFN. <h3>Objectives</h3> To evaluate the efficacy of ANI in real-life under the early access program (09/2021 – 03.2022). <h3>Methods</h3> A total of seven patients (all female, mean age 50 years, disease duration 15 years) with SLE- diagnosis based on ACR1997 or SLICC or EULAR/ACR 2019 classification criteria for SLE and inadequate response to prior immunosuppressive therapies received ANI from 09/2021 until 03.2022 as part of an early access program. Patients' demographics, clinical and laboratory characteristics, disease activity (SLEDAI-2K, CLASI) were recorded at baseline and first months of the administration of ANI. <h3>Results</h3> Active skin disease was the dominant clinical manifestation of all patients for the administration of ANI (subacute cutaneous lupus in 6/7, discoid lupus in 3/7, severe chemeltular lesions in one patient). Patients had received an average of 5.1 immunosuppressive drugs before ANI, with an inadequate response. The mean (SD) SLEDAI index at baseline was 6.9 (1.1) and the mean (SD) prednisone dose 2.7 (2.8) mg/day. In reference to the skin disease, mean (SD) CLASI (Activity/Damage) before first administration of ANI was 9.9/1.4 (6.3)/(2.2). A rapid response of the skin disease, especially the subacute cutaneous lupus lesions, was observed from the first injection of ANI. As expected, the results were less prominent in patients who had discoid lupus lesions, although patients reported subjective improvement. The mean (SD) SLEDAI, CLASI and daily prednisone dose are 3.4 (1.8), 3/1.4 (1.4/2.2) and 2.5 (2.5) mg, respectively. After a mean (SD) follow-up of 5.7 (2.0) months, one patient discontinued ANI due to VZV infection. <h3>Conclusion</h3> IFN inhibition is effective for the treatment of refractory cutaneous lupus manifestations. The prompt response of the dermatologic disease to ANI likely reflects the beneficial effects of neutralization of IFN on the autoimmune and vasculopathic processes in SLE. <h3>References</h3> [1]Furie R et al- Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus, Arthritis Rheumatol. 2017 Feb;69(2):376-386 [2]Rodero, MP et al -Type I interferon–mediated monogenic autoinflammation: The type I interferonopathies, a conceptual overview, J Exp Med 2016; 2013(12): 2527-38 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB1461 COLCHICINE INTOLERANT FAMILIAL MEDITERRANEAN FEVER PATIENTS RECEIVING IL-1 ANTAGONISTS: DO THEY MISS ADVANTAGE OF COMBINATION
Authors: D. Yildirim, B. Özkiziltaş, I. Vasi, R. C. Kardaş, R. Duran, H. Karadeniz, A. Avanoglu Guler, H. Küçük, A. Erden, B. Goker, M. Ozturk, A. Tufan
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Colchicine is the mainstay of Familial Mediterranean Fever treatment, whereas interleukin-1 antagonists (IL1A) are the treatment of choice in refractory or intolerant cases [1,2]. <h3>Objectives</h3> Aim of the study was to evaluate clinical and laboratory processes and damage status of FMF patients who colchicine resistant and/or intolerant and compare them with FMF patients who got effective doses. <h3>Methods</h3> A total of 125 patients diagnosed as FMF and treated with IL-1 antagonists were enrolled to the study. Study population was divided into two group according to the use of colchicine group 1 was consisted of 96 patients treated with IL1A+colchicine combination and group 2 was 29 patients only treated with IL1A due to resistance and/or intolerance to colchicine. Demographic, clinical and laboratory features were compared between tretament groups. <h3>Results</h3> Clinical activity and damage scores were similar between groups. Damage parameters were also assesed seperately and showed significantly higher rate of disease related amenorrhea in those patients terated with IL1A alone (p=0,017). <h3>Conclusion</h3> We concluded that colchicine should be added to treatment but colchicine resistant or intolerant FMF patients may be effectively treated with IL-1 antagonists alone. <h3>References</h3> [1]Tufan A, Lachmann HJ. Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review. Turk J Med Sci. 2020 Nov 3;50(SI-2):1591-1610. [2]Varan Ö, Kucuk H, Babaoglu H, Guven SC, Ozturk MA, Haznedaroglu S, Goker B, Tufan A. Efficacy and safety of interleukin-1 inhibitors in familial Mediterranean fever patients complicated with amyloidosis. Mod Rheumatol. 2019 Mar;29(2):363-366. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS1113 PROFILING OF SYSTEMIC IMMUNE RESPONSES IN AXIAL SPONDYLOARTHRITIS PATIENTS REVEALS STRIKINGLY DISTINCT CELLULAR AND MOLECULAR MECHANISMS OF ACTION OF IL-17A INHIBITORS AND TNF-BLOCKERS
Authors: N. Rosine, S. Koturan, V. Guillemot, C. Leloup, F. Veress, T. Stephen, H. Yahia, J. Sellam, F. Berenbaum, N. Pietrosemoli, E. Bianchi, C. Miceli Richard, L. Rogge
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> IL-17A inhibitors (IL-17i) and TNF-inhibitors (TNFi) are currently the only biologic drugs available as first line treatment in axial spondyloarthritis (axSpA). While several studies have provided mechanistic insights into TNFi action, much less is known how IL-17i affect immune responses in patients. <h3>Objectives</h3> We have compared the effects of IL-17i and TNFi on immune cell frequencies and induced immune responses to obtain information about the mechanisms of action of these two drugs in axSpA patients <i>in vivo</i>. <h3>Methods</h3> Induced immune responses to microbial and pathway-specific stimuli were analyzed in peripheral blood samples from 40 axSpA patients before and after IL-17i or TNFi treatment, using highly standardized whole-blood stimulation assays. Changes in gene expression were determined by RNA sequencing and secreted molecules were measured using proximity ligation assays. <h3>Results</h3> IL-17A-blockade had very limited effects on systemic immune responses with no significant gene expression changes detectable in stimulated whole-blood cultures when comparing samples before and 16 weeks after treatment initiation. In contrast, anti-TNF therapy induced profound changes in patients' immune responses affecting the expression of more than 4000 genes. Pathways analysis revealed major effects of TNFi on the expression of genes involved in protection from bacterial (Tuberculosis, Legionellosis), viral (EBV, Influenza) and parasitic (Leishmaniasis, Toxoplasmosis) infections (Figure 1). Analysis of secreted inflammatory cytokines and chemokines showed that TNF-blockade also strongly affected innate and adaptive immune cell signaling, while only minor changes were observed in stimulation cultures from IL-17i-treated axSpA patients. Furthermore, we noted major effects of TNFi, but not of IL-17i, on neutrophil and monocyte counts in the circulation of treated patients. <h3>Conclusion</h3> We show that the two currently used biotherapies of axSpA act by strikingly distinct cellular and molecular mechanisms. While anti-TNF therapy has major effects on systemic immune responses with potential implications for increased susceptibility to infectious microorganisms, IL-17 inhibitors had a lesser impact on systemic immune responses compared to TNFi, suggesting that may rather act on non-immune cells and/or in inflamed tissues. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0533 EFFECT OF RENIN-ANGIOTENSIN SYSTEM INHIBITORS ON RENAL REMISSION IN LUPUS NEPHRITIS: A REAL-WORLD SINGLE-CENTER STUDY
Authors: X. Zhang, H. Huang, Y. Fan, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Renin-angiotensin-system inhibitors (RASi) reduce urinary protein excretion and protect renal function in both diabetic and nondiabetic nephropathy. Few studies have focused on RASi in LN patients. <h3>Objectives</h3> The study aimed to provide real-world evidence to assess the effect of RASi in LN patients. <h3>Methods</h3> A total of 233 LN patients were included; 155 were RASi users, and 78 were not. The rate of proteinuria partial recovery (PPR), complete remission (CR), total remission (TR), the decline and decline rate of proteinuria at 6 and 12 months were compared by Chi-square test and Kaplan‒Meier analysis. Propensity score matching (PSM) and Cox regression analysis was performed. <h3>Results</h3> The cumulative rates of PRR, TR and CR were 133 (85.8%), 103 (66.9%), and 53 (34.2%) in the RASi group compared to 66 (87.7%), 55 (71.1%), and 44 (57.2%) in the no RASi group at 6 months, respectively. At 12 months, the cumulative rates of PRR, TR and CR were 144 (99.4%), 115 (76.1%), and 83 (56.0%) in the RASi group and 73 (97.3%), 64 (83.5%) and 54 (71.3%) in the no RASi group, respectively. There was no statistically significant difference in cumulative PRR and TR rates between the two groups (p=0.601 and 0.203). The cumulative CR rate was significantly higher in the no RASi group (p=0.001). The UTP level of the RASi group was consistently higher than that of the no RASi group at 6 [0.5(0.2,1.6) vs. 0.3(0.1,0.7), p=0.003) and 12 months [0.2(0.1,0.6) vs. 0.1(0.1,0.3), p=0.008]. However, the ΔUTP was significantly higher in the RASi group [6 months: 2.6 (1.3, 5.1) vs. 1.2 (0.8, 2.4), p=0.001; 12 months: 3.3 (1.6, 5.4) vs 1.4 (0.9, 2.9), p=0.001], and the decline rate did not reach significance. Meanwhile, the serum SCr showed no difference between the two groups. The results were similar after PSM. Only HCQ usage was a prognostic predictor of PRR (HR 2.110, 95% CI: 1.223, 3.642, p=0.007). <h3>Conclusion</h3> RASi may not benefit the renal remission of LN, and the results need to be interpreted with caution. However, RASi may help to decrease urinary protein. Further high-quality randomized controlled trials are required to evaluate the RASi effects on proteinuria and renal prognosis. <h3>References</h3> [1]Agodoa, L. Y. Appel, L. Bakris, G. L,et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial; JAMA(2001) 285,21,2719-28. [2]S. Dura´n-Barraga´n, G. McGwin Jr, et al. Angiotensin-converting enzyme inhibitors delay the occurrence of renal involvement and are associated with a decreased risk of disease activity in patients with systemic lupus erythematosus—results from LUMINA (LIX): a multiethnic US cohort. Rheumatology (2008) 47:1093–1096. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS1411 ASSESSING THE CAUSALITY OF GAMMA (IFN-Γ) AND IFN-Γ RECEPTOR 1/2 (IFNΓR1/2) WITH SYSTEMIC LUPUS ERYTHEMATOSUS RISK USING GENETIC DATA
Authors: K. X. Yao, Y. Q. Long, L. L. Qiao, J. Qiao, S. X. Zhang, C. Wang, X. LI
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a chronic multisystem auto-immune disease with extremely varied clinical manifestations and a complex pathogenesis <sup>[1]</sup>. Past studies have shown that the Interferon gamma（IFN-γ) signaling pathway is activated in SLE patients and that its proper functioning is inextricably associated with Interferon gamma receptor 1（IFN-γR1）and Interferon gamma receptor 2（IFN-γR2). However, the causal relationship between IFN-γ, IFN-γR1, and IFN-γR2 and the risk of SLE has not been elucidated. <h3>Objectives</h3> This study aims to assess the causal association between IFN-γ, IFN-γR1 and IFN-γR2 and SLE disease within a bidirectional Mendelian-randomization design <sup>[2]</sup>. <h3>Methods</h3> Genetic instruments of exposure to IFN-γ, IFN-γR1 and IFN-γR2 were derived from the large genome-wide association study (GWAS) which included a total of 3,301 sample size with Males and Females. Instrumental variables for SLE was selected from another independent GWAS analysis which comprised 5,201 cases and 9,066 controls with European ancestry. Bi-directional two-sample MR was performed using inverse variance weighting (IVW), MR-Egger regression and weighted median methods. A series of sensitivity analyses was conducted to assess the robustness of the results. <h3>Results</h3> The IVW results showed that IFN-γ had a positive causal association with the risk of SLE [OR 1.24 (95% CI 0.85, 2.26), P = 0.018]. And IFN-γR2 was found to have negatively correlation with the onset of SLE [OR 0.85(95% CI 0.73, 0.99), P = 0.034]. However, no genetic association was detected between IFN-γR1 and SLE [OR 0.97 (95% CI 0.79, 1.19), P = 0.768]. Evidence from bidirectional MR did not support reverse causality. Weighted median regression also showed directionally similar estimates. Both funnel plots and MR-Egger intercepts suggest no directional pleiotropic effects observed. <h3>Conclusion</h3> In conclusion, MR analyses found that higher levels of IFN-γ or lower level of IFN-γR2 is significantly associated with increased risk of SLE, suggesting that IFN-γR2 are potential therapeutic targets for the treatment of SLE. <h3>References</h3> [1]A Fanouriakis, N Tziolos, G Bertsias, DT Boumpas. Update omicronn the diagnosis and management of systemic lupus erythematosus. <i>Ann Rheum Dis</i> 2021;80(1):14-25. [2]NM Davies, MV Holmes, SG Davey. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. <i>BMJ</i> 2018;362:k601. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.